Chromatography is a well-established and valuable technique in both preparative and analytical work as well as in purification generally. Typical industrial chromatography apparatus has an upright housing, or column, in which a bed of packing material, usually a particulate medium, rests against a permeable retaining layer. Fluid mobile phase enters through an inlet e.g. at the top of the column, usually through a porous, perforated, mesh or other restricted-permeability layer, moves through the packed bed and is taken out at an outlet, typically below a restricted-permeability layer.
The bed of packing material is usually filled in the column by applying a defined amount of a slurry of the medium to the column and settling the medium in the column by a liquid flow through the column. Knowledge of slurry concentration is very vital when packing columns at any scale but foremost at pilot to process scale so that the correct amount of media can be transferred to the column. This is necessary to achieve the correct bed height at the correct compression in a reproducible manner. This is currently one of the most poorly controlled aspects of column packing and causes many failed attempts.
Today, slurry concentration is often measured by gravity settling in a graduated cylinder overnight. This requires planning and accuracy, which is often lacking. In addition, many media do not settle fully after overnight settling which is standard but requires longer time. This is often neglected and the measured slurry concentration often deviates much from the correct value. The use of different buffers can also cause the medium to settle differently.
There is therefore a need for means which may simplify the concentration determination as well as increase the determination quality which introduces less variation in the process by varying bed compression, bed height or both.